Evidence of CD8+ T-cell-mediated selective pressure on human immunodeficiency virus type 1 nef in HLA-B*57+ elite suppressors.
Elite suppressors (ES) are human immunodeficiency virus type 1 (HIV-1)-infected patients who maintain viral loads of <50 copies/ml without treatment. The observation that the HLA-B*57 allele is overrepresented in these patients implies that HIV-1-specific CD8(+) T cells play a key role in suppressing viral replication. We have previously shown that while CD8(+) T-cell escape mutations are rarely seen in proviral Gag sequences in resting CD4(+) T cells from peripheral blood, they are present in every clone amplified from the low levels of free virus in the plasma of HLA-B*57(+) ES. In this study, we compared the pattern of mutations in Nef sequences amplified from peripheral blood CD4(+) T cells and from plasma virus. We show that Nef mutations are present in plasma virus but are rare in the cellular sequences and provide evidence that these plasma Nef variants represent novel escape mutants. The results provide further evidence of CD8(+) T-cell-mediated selective pressure on plasma virus in ES and suggest that there must be ongoing HIV-1 replication in spite of the very low viral loads seen for these patients.
Bailey
Justin R
JR
Broadway Research Bldg., Rm. 880, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA. jblanks@jhmi.edu
Brennan
Timothy P
TP
O'Connell
Karen A
KA
Siliciano
Robert F
RF
Blankson
Joel N
JN
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016000:Cluster Analysis; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1